This invention was made with Government support under Grant No. CA-44848, awarded by the National Institutes of Health. The Government has certain rights in this invention.
1. Field of the Invention
The present invention relates generally to marine bacteria which produce anti-biotics, anti-inflammatory agents and associated pharmacologically-active compounds. More particularly, the present invention relates to the discovery and isolation of a particular marine bacterium which, when subjected to fermentation in seawater-based media, is capable of producing a cyclic heptapeptide that is an effective anti-biotic and anti-inflammatory agent.
2. Description of Related Art
There is a growing interest in investigating diverse classes of marine bacteria to determine their ability to produce secondary metabolites that are useful as drugs or pharmaceutical agents. Terrestrial actinomycetes are one type of bacteria which are known to produce a large number of antibiotic and associated compounds. Related bacteria are known to exist in various marine habitats including the surfaces of marine animals and plants (Fenical, W. Chem. Rev. 1993, 93, 1673-1683; Gil-Turnes, M. S., Hay, M. E., Fenical, W. Science 1989, 246, 116-118; and Gil-Turnes, M. S., Fenical, W. Biol. Bull. 1992, 182,105-108). The actinomycetes are also found in shallow water marine sediments (see Jensen, P. R., Dwight, R., Fenical, W. Appl. Environ. Microbiol. 1991, 37, 1107-1108).
Some of the secondary metabolites produced by marine actinomycetes have been found to possess antibiotic properties. For example, see Pathirana, C., Jensen, P. R., Fenical, W. Tetrahedron Lett. 1993, 33, 7663-7666; Pathirana, C., Jensen, P. R., Dwight, R., Fenical, W. J. Org. Chem. 1992, 57, 740-742; and Okami, Y., Hopita, K., Yoshida, M., Ikoda, D., Kondo, S., Umozawa, H. J. Antibiot. 1979, 32, 964-966. Other secondary metabolites have been found to possess antitumor properties (see Tapiolas, D. M., Roman, M., Fenical, W., Stout, T. J., Clardy, J. J. Am. Chem. Soc. 1991, 115, 4682-4683; and Takahashi, A., Kurosawa, S., Ikeda, D., Okami, Y., Takeuchi, T. J. Antibiot. 1989, 42, 1556-1561).
Although some marine bacteria have been isolated which are capable of producing antibiotics and antitumor agents, there is a continuing need to discover and isolate additional marine bacteria that are capable of producing secondary metabolites which are useful as pharmaceutical agents. In addition, there is a continuing need to provide new methods for fermenting marine bacteria to optimize production of useful secondary metabolites.